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DOI 10.1038/s41375-025-02667-7

Медицинская библиотека · Leukemia · 2025

Disease-specific U1 spliceosomal RNA mutations in mature B-cell neoplasms.

Nadeu Ferran, Shuai Shimin, Clot Guillem, Hilton Laura K, Diaz-Navarro Ander, Martín Silvia, Royo Romina, Baumann Tycho, Kulis Marta, López-Oreja Irene, Cossio Manuel, Lu Junyan, Ljungström Viktor, Young Emma, Plevova Karla, Knisbacher Binyamin A, Lin Ziao, Hahn Cynthia K, Bousquets Pablo, Alcoceba Miguel, González Marcos, Colado Enrique, Payer Ángel R, Aymerich Marta, Terol María J, Rivas-Delgado Alfredo, Enjuanes Anna, Ruiz-Gaspà Sílvia, Chatzikonstantinou Thomas, Hägerstrand Daniel, Jylhä Cecilia, Skaftason Aron, Mansouri Larry, Stranska Kamila, Doubek Michael, van Gastel-Mol Ellen J, Davis Zadie, Walewska Renata, Scarfò Lydia, Trentin Livio, Visentin Andrea, Parikh Sameer A, Rabe Kari G, Moia Riccardo, Armand Marine, Rossi Davide, Davi Frederic, Gaidano Gianluca, Kay Neil E, Shanafelt Tait D, Ghia Paolo, Oscier David, Langerak Anton W, Beà Sílvia, López-Guillermo Armando, Neuberg Donna, Wu Catherine J, Getz Gad, Pospisilova Sarka, Stamatopoulos Kostas, Rosenquist Richard, Huber Wolfgang, Zenz Thorsten, Colomer Dolors, Martín-Subero José I, Delgado Julio, Morin Ryan D, Stein Lincoln D, Puente Xose S, Campo Elías

СтатьяПоддержка исследования: вне правительства СШАПоддержка NIH: внешняя программаПеревод в очереди

Аннотация

Recurrent mutations in the third base of U1 spliceosomal RNA responsible for marked splicing and expression abnormalities have been described in chronic lymphocytic leukemia (CLL) and some solid tumors. However, the clinical significance of these mutations in large and independent CLL cohorts as well as their presence in other B-cell neoplasms is unknown. Here we characterized U1 mutations in 1670 CLL and 363 mature B-cell lymphomas. We confirmed that the g.3A>C U1 mutation is found in 3.5% of CLL, which conferred rapid disease progression independently of the main biological and clinical prognostic markers of the disease. Additionally, a recurrent g.9C>T mutation was found in 1.5% of CLL causing downstream splicing alterations and associated with adverse prognosis. We also identified a g.4C>T mutation in 10% of diffuse large B-cell lymphomas of the germinal center subtype and a g.7A>G mutation in 30% of EBV-negative Burkitt lymphomas, both of which altered the splicing pattern of multiple genes. This study reveals novel, recurrent, and tumor-specific U1 mutations in mature B-cell neoplasms with biological and prognostic implications, thus establishing U1 as a novel pan-B-cell malignancy driver gene.

Для цитирования: Nadeu Ferran, Shuai Shimin, Clot Guillem, Hilton Laura K, Diaz-Navarro Ander, Martín Silvia, Royo Romina, Baumann Tycho, Kulis Marta, López-Oreja Irene, Cossio Manuel, Lu Junyan, Ljungström Viktor, Young Emma, Plevova Karla, Knisbacher Binyamin A, Lin Ziao, Hahn Cynthia K, Bousquets Pablo, Alcoceba Miguel, González Marcos, Colado Enrique, Payer Ángel R, Aymerich Marta, Terol María J, Rivas-Delgado Alfredo, Enjuanes Anna, Ruiz-Gaspà Sílvia, Chatzikonstantinou Thomas, Hägerstrand Daniel, Jylhä Cecilia, Skaftason Aron, Mansouri Larry, Stranska Kamila, Doubek Michael, van Gastel-Mol Ellen J, Davis Zadie, Walewska Renata, Scarfò Lydia, Trentin Livio, Visentin Andrea, Parikh Sameer A, Rabe Kari G, Moia Riccardo, Armand Marine, Rossi Davide, Davi Frederic, Gaidano Gianluca, Kay Neil E, Shanafelt Tait D, Ghia Paolo, Oscier David, Langerak Anton W, Beà Sílvia, López-Guillermo Armando, Neuberg Donna, Wu Catherine J, Getz Gad, Pospisilova Sarka, Stamatopoulos Kostas, Rosenquist Richard, Huber Wolfgang, Zenz Thorsten, Colomer Dolors, Martín-Subero José I, Delgado Julio, Morin Ryan D, Stein Lincoln D, Puente Xose S, Campo Elías. Disease-specific U1 spliceosomal RNA mutations in mature B-cell neoplasms.. Leukemia. 2025. DOI: 10.1038/s41375-025-02667-7.

Предметные рубрики MeSH

HumansMutationPrognosisLeukemia, Lymphocytic, Chronic, B-CellSpliceosomesLymphoma, B-CellRNA, Small NuclearMaleFemaleRNA SplicingMiddle AgedLymphoma, Large B-Cell, Diffuse
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